Fabrication of Nanobiosensor for Early Detection of Cancer Biomarker

Abstract

The common problem with all different forms of cancer is that many people experience the symptoms, and have it diagnosed when it is too late. Nanobiosensors have become essential tools in early cancer biomarker detection and quantification, in which nanoprobe materials and composition play crucial roles in achieving sensitive and stable detection. Although nanobiosensing techniques are proved to be robust and efficient, most of them are time-consuming and still suffer from the lack of accuracy and sensitivity for clinical diagnostics. This thesis aimed to address these shortcomings by developing a new class of hybrid nanobiosensing platform based on low dimensional materials with niche electro-optical properties and favorable surface chemistry. The multifunctional carbon nanomaterials (core optical element), named as Carbon Dots (CDs), were engineered through a systematic hydrothermal reaction to achieve the right affinity features for conjugation to a wide range of macromolecules (e.g., peptides and proteins) and polymers (e.g., hydrogels). The hybrid nanobiosensor arrays (named as PACD) employing a family of helix-loop-helix polypeptides de novo, carbon, and gold nanomaterials were fabricated through a step-wise covalent self-nanoassembly. This method is based on matrilysin-digestible peptides (i.e. JR2EC) that are anchored between gold nanoparticle (AuNPs) cores (~30-50 nm) and carbon quantum dot (CDs) satellites (~2-7 nm). The AuNP–CDs produce ideal optical signals, with noticeable fluorescence quenching effects. Upon peptide cleavage by matrilysin, CDs leave the surface of gold nanoparticles, resulting in ultra-fast (nearly 30 seconds) detectable violet and visible fluorescent signals at the limit of detection of 30 nM. The overall knowledge of the underpinnings of synthesizing low-dimensional materials, synthetic bioreceptors and the modular self-assembled nanoarchitectures will make it possible to aim for a universal-multifunctional platform for multiplex detection of several diseases, targeted drug delivery, and drug discovery.